Unidad de Dismorfología, Unidad de Gestión Clínica de Pediatría, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
Adv Ther. 2020 May;37(Suppl 2):25-28. doi: 10.1007/s12325-019-01177-0. Epub 2020 Mar 31.
Metabolic skeletal dysplasias comprise an extensive group of diseases capable of causing changes, usually progressive, in the bone and are due to hereditary disorders in many cases. The diagnosis and treatment of these diseases are not without difficulty, both because of their rarity and their possible confusion with more common diseases. A paradigmatic case of these metabolic skeletal dysplasias is X-linked hypophosphataemic rickets, which causes phosphaturia, a condition that alters the phosphate-calcium metabolism balance consequently causing, among other conditions, skeletal deformities and short stature. The genetic advances in recent years allow a much more accurate diagnosis of this disease when suspected, making differential diagnosis easier with similar entities but whose real causes are different. A better understanding of the phosphate-calcium metabolism allows us to replace the symptomatic treatment currently available with one that involves rebalancing the excess of fibroblast growth factor 23 (FGF23) by using monoclonal antibodies. In November 2018, a symposium sponsored by Kyowa Kirin Pharmaceuticals took place in Madrid, in which national and international experts addressed several aspects of these rare kidney diseases. Some topics addressed were the present and future genetic diagnosis, the use of multi-gene panels in renal or skeletal diseases, the role of animal models to better understand underlying skeletal changes, and the role of conventional radiology and surgery in the diagnosis and final treatment of bone deformities; all these without forgetting the important role of FGF23 and Klotho imbalances that result in the genetic change causing this disease. The optimization and limitations of conventional treatments currently available was also a topic addressed extensively, as well as the implications that new treatments against FGF23 could have in the future. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by the author.
代谢性骨骼发育不良是一组广泛的疾病，能够导致骨骼的变化，通常是进行性的，并且在许多情况下是由于遗传性疾病引起的。这些疾病的诊断和治疗并不容易，既因为它们的罕见性，也因为它们可能与更常见的疾病混淆。这些代谢性骨骼发育不良的典型病例是 X 连锁低磷血症性佝偻病，它会导致磷酸尿，这种情况会改变磷-钙代谢平衡，从而导致骨骼畸形和身材矮小等病症。近年来的遗传进展使得在怀疑患有这种疾病时能够进行更准确的诊断，从而更容易与类似的实体进行鉴别诊断，但这些实体的真正原因是不同的。对磷-钙代谢的更好理解使得我们能够用一种更有效的方法来替代目前的对症治疗，这种方法涉及通过使用单克隆抗体来重新平衡成纤维细胞生长因子 23（FGF23）的过剩。2018 年 11 月，Kyowa Kirin 制药公司在马德里举办了一次研讨会，邀请了国内外专家讨论了这些罕见肾脏疾病的几个方面。讨论的一些主题包括目前和未来的基因诊断、在肾脏或骨骼疾病中使用多基因面板、动物模型在更好地理解潜在骨骼变化中的作用、以及传统放射学和手术在诊断和最终治疗骨骼畸形中的作用；所有这些都没有忘记 FGF23 和 Klotho 失衡在导致这种疾病的遗传变化中所起的重要作用。目前可用的常规治疗方法的优化和限制也是一个广泛讨论的话题，以及针对 FGF23 的新治疗方法在未来可能产生的影响。本文基于之前进行的研究，不包含作者进行的任何新的涉及人类参与者或动物的研究。
